The focus of this Program Project is the motor nerve cell and its susceptibility to disease. The Program combines direct studies of patients with amyotrophic lateral sclerosis (ALS) and basic in vitro tissue culture and in vivo animal studies related to motor neuron biology and pathology. The cental resource is a large clinic devoted to the care and study of ALS patients. Both sporadic and familial forms of ALS are represented. Specific areas of study in this Program include defining properties of motor nerve cells and the neuromuscular junction in health and disease using immunochemical, molecular biologic and physiologic techniques; characterizing muscle and glial cell-derived motor neuron trophic factors, determining the bases of neuronal viral tropism, and evaluating the feasibility of transplantation of motor nerve cells.